242 research outputs found
Innovation in Pain Management
No full textThe transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 12 December 2002.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2004.©The Trustee of the Wellcome Trust, London, 2004.All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Unrelieved pain caused by cancer is experienced by more than 5 million people worldwide, and over the past 50 years has been accepted as unnecessary by both clinicians and politicians. Major innovations in the understanding of pain and our ability to treat it have been made. This Witness Seminar, chaired by Professor David Clark, describes the development of pain clinics, the introduction of the hospice in Britain, and global implementation of innovative technologies for cancer pain relief and advances in research during the latter part of the twentieth century. International health planners argue that the outstanding challenge is to put this knowledge into practice in healthcare settings around the world, often where resources are limited. Reynolds L A, Tansey E M. (eds) (2004) Innovation in pain management, Wellcome Witnesses to Twentieth Century Medicine, vol. 21. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at University College London is funded by the Wellcome Trust,which is a registered charity, no. 210183
Pro-opiomelanocortin neurons in the nucleus of the solitary tract mediate endorphinergic endogenous analgesia in mice
No full textThe nucleus of the solitary tract (NTS) contains pro-opiomelanocortin (POMC) neurons that are 1 of the 2 major sources of β-endorphin in the brain. The functional role of these NTSPOMC neurons in nociceptive and cardiorespiratory function is debated. We have shown that NTSPOMC optogenetic activation produces bradycardia and transient apnoea in a working heart–brainstem preparation and chemogenetic activation with an engineered ion channel (PSAM) produced opioidergic analgesia in vivo. To better define the role of the NTSPOMC neurons in behaving animals, we adopted in vivo optogenetics (ChrimsonR) and excitatory/inhibitory chemogenetic DREADD (hM3Dq/hM4Di) strategies in POMC-Cre mice. We show that optogenetic activation of NTSPOMC neurons produces time-locked, graded, transient bradycardia and bradypnoea in anaesthetised mice that is naloxone sensitive (1 mg/kg, i.p.), suggesting a role of β-endorphin. Both optogenetic and chemogenetic activation of NTSPOMC neurons produces sustained thermal analgesia in behaving mice that can be blocked by naloxone. It also produced analgesia in an inflammatory pain model (carrageenan) but not in a neuropathic pain model (tibial nerve transection). Inhibiting NTSPOMC neurons does not produce any effect on basal nociception but inhibits stress-induced analgesia (unlike inhibition of arcuate POMC neurons). Activation of NTSPOMC neuronal populations in conscious mice did not cause respiratory depression, anxiety, or locomotor deficit (in open field) or affective preference. These findings indicate that NTSPOMC neurons play a key role in the generation of endorphinergic endogenous analgesia and can also regulate cardiorespiratory function.<br/
Characteristics of night-time absorption spike events
No full textInternational audienceSudden increases in cosmic radio noise absorption, known as spike events, have been identified as signatures of substorms in the previous studies. Using data from the IRIS (Imaging Riometer for Ionospheric Studies) at Kilpisjärvi, Finland (L~6) more than 450 night-time spike events between 1994 and 2003 have been identified. Spike events fall into four distinct categories based on their structure and the background magnetic activity as indicated by a local westward electrojet (IL index) derived from the IMAGE (International Monitor for Auroral Geomagnetic Effects) magnetometer network as well as Pi2 magnetic pulsations from SAMNET (The UK Sub-Auroral Magnetometer Network). Classifying the types of absorption spikes allows for identification of phenomena such as multiple onsets and pseudobreakups from riometer data. In addition we have studied the statistical variation of absorption spikes and their sub-classes. This includes examining the magnetic local time (MLT) distribution and the seasonal and solar-cycle variation in spike occurrence. Those that seem to represent substorm onsets show a decidedly different MLT variation to those isolated spikes that represent pseudobreakups. The occurrence of spikes during different levels of geomagnetic activity is examined using the Kp index. Wavelet analysis has been used for studying the temporal structure of spikes; also the direction of motion of spike events and localisation of spikes are presented for all events and each sub-class and results are compared with previous studies. Statistical studies are supported with X-ray images of aurora from PIXIE (The Polar Ionospheric X-ray Imaging Experiment) when available
Modeling the relationship between substorm dipolarization and dispersionless injection
No full textSignificant populations of electrons with energies of tens of keV appear in the Earth's inner central plasma sheet during the substorm expansion phase. Increasing observational evidence indicates that these injections begin at a radially narrow but azimuthally extended transition between very stretched and less stretched field lines around 8 RE. In this work we suggest that the tailward retreat of this transition region can be responsible for adiabatic acceleration of electrons which is sufficient to cause ionospheric signatures of the dispersionless injections observed by riometers. To support this mechanism we develop a novel conceptual magnetotail magnetic field model with a few adjustable parameters which can be easily constrained by observations. Our calculations show that a tailward motion of the transition region at the speed of 0.8 R-E/min is required to achieve good agreement with riometer observations
Using HR-pQCT and finite element analysis to inform clinical assessment of distal radius fractures
No full textDistal radius fractures (DRFs) are commonly treated non-operatively with cast immobilization; however, there are no standardized clinical practice guidelines to direct optimal duration of immobilization following a DRF. Finite element (FE) modelling coupled with high-resolution peripheral quantitative computed tomography (HR-pQCT) allows for non-invasive in vivo assessment of bone density and stiffness throughout the fracture healing process, which may inform fracture healing progression and cast removal. Many fracture assessment instruments have been developed for clinical use, but a lack of validation and standardization has led to considerable variability in the assessment of fracture healing. We hypothesized that changes in bone stiffness and bone mineral density measured using HR-pQCT can better inform the duration of casting following a DRF. We aimed to identify clinical assessment instruments that were good predictors of fracture stiffness and could inform cast removal. Participants (n=30) with a stable DRF were followed for two week intervals from the time of fracture until two months post-fracture, then at three months and six months post-fracture. At each follow-up, participants underwent clinical, radiographic, and functional assessments, as well as had their fractured wrist scanned using HR-pQCT. Recovery of bone stiffness during fracture healing was determined from micro-FE (µFE) models generated from HR-pQCT image data. During fracture healing, significant longitudinal changes were found in µFE-estimated stiffness, patient-reported outcomes, grip strength, range of motion (ROM), tenderness, number of cortices healed based on radiographs, and fracture line visibility (p<0.05); however, no significant change was detected in HR-pQCT based total bone mineral density. Grip strength, ROM, and patient-reported outcomes such as the Patient-Rated Wrist Evaluation (PRWE) and the Quick Disability of the Arm, Shoulder and Hand (QuickDASH) questionnaire correlated strongly with µFE-estimated stiffness (0.61≥ rm ≥0.71). Based on µFE-estimated stiffness, PRWE and QuickDASH are the best predictors of stiffness recovery (p<0.05) and may be used to guide duration of cast immobilization in the clinical setting
Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration:A whole cell recording study in situ
No full textSympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing from the CNS to the periphery to reach the target organs. Although previous in vivo and in vitro cell recording studies have explored their electrophysiological characteristics, it has not been possible to relate these characteristics to their roles in cardiorespiratory reflex integration. We used the working heart-brainstem preparation to make whole cell patch clamp recordings from T3-4 SPNs (n = 98). These SPNs were classified by their distinct responses to activation of the peripheral chemoreflex, diving response and arterial baroreflex, allowing the discrimination of muscle vasoconstrictor-like (MVClike, 39%) from cutaneous vasoconstrictor-like (CVClike, 28%) SPNs. The MVClike SPNs have higher baseline firing frequencies (2.52 ± 0.33 Hz vs. CVClike 1.34 ± 0.17 Hz, P = 0.007). The CVClike have longer after-hyperpolarisations (314 ± 36 ms vs. MVClike 191 ± 13 ms, P < 0.001) and lower input resistance (346 ± 49 MΩ vs. MVClike 496 ± 41 MΩ, P < 0.05). MVClike firing was respiratory-modulated with peak discharge in the late inspiratory/early expiratory phase and this activity was generated by both a tonic and respiratory-modulated barrage of synaptic events that were blocked by intrathecal kynurenate. In contrast, the activity of CVClike SPNs was underpinned by rhythmical membrane potential oscillations suggestive of gap junctional coupling. Thus, we have related the intrinsic electrophysiological properties of two classes of SPNs in situ to their roles in cardiorespiratory reflex integration and have shown that they deploy different cellular mechanisms that are likely to influence how they integrate and shape the distinctive sympathetic outputs. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.</p
High-Resolution Study of the Relationship Between the Region 2 Birkeland Current Equatorward Boundary and Soft Electron Fluxes
No full textThe nightside Region 2 (R2) Field Aligned Current (FAC) system is associated with magnetospheric dynamics occurring close to the inner magnetosphere. The current carriers for this system have been studied extensively at higher energies. In this study, we investigate the potential role of electrons in the less studied suprathermal (sub-keV) range. The Enhanced Polar Outflow Probe (e-POP) instrument suite on the CASSIOPE satellite (Swarm Echo) consists of eight plasma instruments, including the Suprathermal Electron Imager (SEI) and the magnetic field instrument (MGF). The SEI records two-dimensional energy-angle images of electron distribution for energies up to 350 eV at a rate of 100 images per second. The MGF samples the magnetic field at a sampling rate of 160 times per second with a resolution of 0.0625 nT. Even though ePOP, whose scientific focus is polar outflow, does not detect high-energy particles (> 1 keV), its polar orbit is optimal for studying current carriers of FACs. We examine suprathermal electron fluxes over the region of 45-80º magnetic latitude during different geomagnetic conditions based on 25 traversals of the R2 boundary. These range from 1700-0400 MLT during which the SEI detects enhanced suprathermal electron fluxes in the 5-100 eV energy range just equatorward of the R2 boundary. Coincident with these fluxes and in a majority of cases, we see evidence of a current in the opposite direction of the R2 current, which we believe has not been reported previously
AKR breakup and auroral particle acceleration at substorm onset
No full textThe dynamical behavior of auroral kilometric radiation (AKR) is investigated in connection with auroral particle acceleration at substorm onsets using high-time-resolution wave spectrograms provided by Polar/PWI electric field observations. AKR develops explosively at altitudes above a preexisting low-altitude AKR source at substorm onsets. This “AKR breakup” suggests an abrupt formation of a new field-aligned acceleration region above the preexisting acceleration region. The formation of the new acceleration region is completed in a very short time (amplitude increases 10,000 times in 30 seconds), suggesting that the explosive development is confined to a localized region. AKR breakups are usually preceded (1–3 minutes) by the appearance and/or gradual enhancement of the low-altitude AKR. This means that the explosive formation of the high-altitude electric field takes place in the course of the growing low-altitude acceleration. The development of the low-altitude acceleration region is thus a necessary condition for the ignition of the high-altitude bursty acceleration. The dH/dt component from a search-coil magnetometer at ground shows that a few minutes prior to substorm onsets, the quasi-DC component begins a negative excursion that is nearly synchronized with the start of the gradual enhancement of the low-altitude AKR, indicating a precursor-like behavior for the substorm. This negative variation of dH/dt suggests an exponentially increasing ionospheric current induced by the upward field-aligned current. At substorm onsets, the decrease in the quasi-DC variation of dH/dt further accelerates, indicating a sudden reinforcement of the field-aligned current
Pc5 modulation of high energy electron precipitation: particle interaction regions and scattering efficiency
No full textInternational audienceUsing the NORSTAR riometer and CANOPUS magnetometer arrays we have investigated the modulation of high energy electron precipitation by ULF waves in the Pc5 frequency band. We conducted two separate studies of Pc5 activity in the riometers. The first is an independent survey of three riometer stations in the Churchill line (one at each sub-auroral, auroral, and typical polar cap boundary latitudes) in which we identified all riometer Pc5-band pulsations over 11 years. All had a corresponding magnetometer pulsation implying that a magnetic pulsation, is a necessary condition for a riometer pulsation (in the Pc5 Band). We find seasonal and latitude dependencies in the occurrence of riometer pulsations. By a factor of two, there are more riometer pulsations occurring in the fall-winter than the spring-summer. At higher latitudes there is a tendency towards noon pulsations during the spring-summer, suggesting that the criteria for riometer pulsations is affected by the dipole tilt. Our second study was based on the previous magnetometer study of Baker et al. (2003). Using the database of Pc5 activity from that study we were able to select the riometer Pc5 pulsations which adhere to the strict Pc5 definition in the magnetometer. We find that roughly 95% of the riometer pulsations occurred in the morning sector compared to 70% in the magnetometer. Given a magnetometer pulsation at Gillam in the morning sector, there is a 70% chance of there being a corresponding riometer pulsation. The morning sector probabilities at Rankin (geomagnetic (PACE) latitude 74°) and Pinawa (61°) are 3% and 5%, respectively. These statistics suggest there is a localized region in the pre-noon magnetosphere where Pc5 band ULF activity can modulate high energy electron precipitation. We also find that riometer pulsations display a Kp selection towards mid (i.e. 3?4) activity levels which mimics the product of the Kp dependence of high-energy electron fluxes on the dawn side (from CRRES) and all magnetic Pc5 activity. A superposed epoch analysis revealed that the elevated electron flux needed to produce a riometer pulsation is most likely provided by substorm injections on the nightside. We also find that the amplitude of modulated precipitation correlates well with the product of the background absorption and the magnetic pulsation amplitude, again leading to the idea that a riometer pulsation needs both favorable magnetospheric electron flux conditions and large enough magnetic Pc5 wave activity. We further separate our pulsations into field line resonances (FLRs), and non-field line resonances (non-FLRs), as identified in the Baker et al. (2003) survey. We find that FLRs are more efficient at modulating particle precipitation, and non-FLRs display an amplitude cutoff below which they do not interact with the high energy electron population. We conclude that the high energy electron precipitation associated with Pc5 pulsations is caused by pitch angle scattering (diffusion) rather than parallel acceleration. We suggest two future studies that are natural extensions of this one. Keywords. Energetic Particles/Precipitating; Wave-Particle Interactions; Auroral Phenomen
FIRST COMPARATIVE SCINTILLATION STUDY USING ARCTIC AND ANTARCTIC GPS RECEIVER ARRAYS
No full textArrays of dual-frequency GPS receivers operating in the Arctic and
Antarctic monitor scintillation and ionospheric total electron content
at high latitudes. Even under solar minimum conditions, events of
significant phase scintillation have been observed in both polar caps.
Climatology studies in both hemispheres show that phase scintillation
as a function of magnetic local time and geomagnetic latitude
primarily occurs in the nightside auroral oval and ionospheric cusp,
with the scintillation regions shifting in latitude in response to
varying geomagnetic activity. Preliminary results from the first
comparative scintillation study supported by ground-based
instruments including HF radars, ionosondes and all-sky imagers are
presented. In the future, in-situ measurements by the Enhanced Polar
Outflow Probe (ePOP) will provide additional support to study the
Arctic and Antarctic ionospheres.UnpublishedBuenos Aires - Argentina3.9. Fisica della magnetosfera, ionosfera e meteorologia spazialeope
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